Modulation of factor 11 expression

Abstract

Disclosed herein are antisense compounds and methods for decreasing Factor 11 and treating or preventing thromboembolic complications in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to Factor 11 include thrombosis, embolism, and thromboembolism, such as, deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke. Antisense compounds targeting Factor 11 can also be used as a prophylactic treatment to prevent individuals at risk for thrombosis and embolism.

What is claimed is: 
     
         1 . A method comprising administering to an animal having or at risk for developing a thromboembolic complication a therapeutically effective amount of a compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence that is at least 90% complementary to Factor 11 nucleic acid or a salt thereof; wherein the administering treats or prevents the thromboembolic complication in the animal; and wherein the administering does not induce intracerebral hemorrhage in the animal. 
     
     
         2 . The method of  claim 1 , wherein the thromboembolic complication is any of the group consisting of deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke. 
     
     
         3 . The method of  claim 1 , wherein the compound is for co-administration with any of aspirin, clopidogrel, dipyridamole, heparin, lepirudin, ticlopidine, warfarin, apixaban, rivaroxaban, LOVENOX, and Factor Xa inhibitor. 
     
     
         4 . The method of  claim 1 , wherein the compound is for concomitant administration with any of aspirin, clopidogrel, dipyridamole, heparin, lepirudin, ticlopidine, warfarin, apixaban, rivaroxaban, LOVENOX, and Factor Xa inhibitor. 
     
     
         5 . The method of  claim 1 , wherein the compound consists of a single-stranded modified oligonucleotide. 
     
     
         6 . The method of  claim 5 , wherein at least one internucleoside linkage of the compound is a modified internucleoside linkage. 
     
     
         7 . The method of  claim 6 , wherein each internucleoside linkage of the compound is a phosphorothioate internucleoside linkage. 
     
     
         8 . The method of  claim 7 , wherein at least one nucleoside of the compound comprises a modified sugar. 
     
     
         9 . The method of  claim 8 , wherein the modified sugar is a bicyclic sugar. 
     
     
         10 . The method of  claim 9 , wherein the bicyclic sugar comprises a 4′-(CH 2 ) n —O-2′ bridge, wherein n is 1 or 2. 
     
     
         11 . The method of  claim 9 , wherein the bicyclic sugar comprises a 4′-CH(CH 3 ) n —O-2′ bridge. 
     
     
         12 . The method of  claim 8 , wherein the modified sugar comprises a 2′-O-methoxyethyl group. 
     
     
         13 . The method of  claim 8 , wherein at least one nucleoside of the compound comprises a modified nucleobase. 
     
     
         14 . The method of  claim 13 , wherein the modified nucleobase is a 5-methylcytosine. 
     
     
         15 . The method of  claim 1 , wherein the modified oligonucleotide comprises:
 a gap segment consisting of linked deoxynucleosides;   a 5′ wing segment consisting of linked nucleosides;   a 3′ wing segment consisting of linked nucleosides, wherein the gap segment is positioned immediately adjacent to and between the 5′ wing segment and the 3′ wing segment, and wherein each nucleoside of each wing segment comprises a modified sugar.   
     
     
         16 . The method of  claim 15 , wherein the modified oligonucleotide consists of 20 linked nucleosides. 
     
     
         17 . The method of  claim 1 , wherein the modified oligonucleotide comprises:
 a gap segment consisting of ten linked deoxynucleosides;   a 5′ wing segment consisting of five linked nucleosides;   a 3′ wing segment consisting of five linked nucleosides, wherein the gap segment is positioned immediately adjacent and between the 5′ wing segment and the 3′ wing segment, wherein each nucleoside of each wing segment comprises a 2′-O-methoxyethyl sugar, wherein each internucleoside linkage of the modified oligonucleotide is a phosphorothioate linkage, and wherein each cytosine of the modified oligonucleotide is a 5-methylcytosine.   
     
     
         18 . The method of  claim 17 , wherein the modified oligonucleotide consists of 20 linked nucleosides.